Abstract
mir-101-3p has been reported to be a tumor suppressor and a promising therapeutic target in cancer. Recently, AMPK dysfunction has been highlighted in cancers, including breast cancer. The aim of this study is to investigate the biological roles of mir-101-3p and AMPK in breast cancer. Our research demonstrated that AMPK was up-regulated in breast cancer tissues and cell lines, especially in triple negative breast cancer (TNBC). High-expression of AMPK correlated with poor outcome in both total breast cancer and TNBC patients. Ectopic expression of AMPK improved glucose uptake, glycolysis, proliferation of TNBC cells in vitro and its tumorigenicity in vivo. AMPK was predicted to be a direct target of mir-101-3p. The luciferase reporter assay was performed to certificate this prediction. The expression of AMPK was suppressed by transfection of mir-101-3p in TNBC cells. Over-expression of mir-101-3p or knock-down of AMPK inhibited glucose metabolism and proliferation of TNBC cells in vitro. Our study provides evidence that mir-101-3p- AMPK axis could be a promising therapeutic target in TNBC targeting tumor metabolism.
Highlights
Breast cancer is the most common female malignancy worldwide, with about 240,000 new incidence per year in US [1]
We investigated the expression of AMPK and its prognostic roles in breast cancer patients, predicted and further identified AMPK as a novel target of mir-101-3p in triple negative breast cancer (TNBC). mir-101-3p-AMPK axis could be a key regulator of tumor metabolism and progression in TNBC
These results suggest that increased AMPK expression is a frequent event in human breast cancer tissues, especially in TNBC
Summary
Breast cancer is the most common female malignancy worldwide, with about 240,000 new incidence per year in US [1]. The diagnosis and therapy of breast cancers could depend on the TNM staging system [2] and their molecular biomarkers [3], including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2) in major. TNBC patients would predict more distant metastasis, tumor recurrence, and therapy resistance [4,5,6]. To find efficient therapeutic targets remains an emergency for TNBC patients [7]. Mir-101, with its two precursor hairpin structures transcribed from chromosome 1 and 9 separately in human [8], has been associated with carcinogenesis and cancer therapy recently [9, 10]. Mir-101-3p directly targeted MCL-1, inhibiting cell progression and enhancing paclitaxel sensitivity in TNBC [18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
